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Research Express@NCKU - Articles Digest
Research Express@NCKU Volume 29 Issue 1 - April 24, 2015
[ http://research.ncku.edu.tw/re/articles/e/20150424/2.html ]
In vivo anti-cancer efficacy of magnetite nanocrystal based system using locoregional hyperthermia
combined with 5-fluorouracil chemotherapy
Tsung-Ju Lia, Chih-Chia Huangb,c,e, Pin-Wei Ruanb, Kuei-Yi Chuangb, Kuang-Jing Huangd, DarBin Shieha,d,e,* , Chen-Sheng Yehb,e
a Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan
b Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan
c Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University,
Taipei 112, Taiwan
d Institute of Oral Medicine, National Cheng Kung University Hospital, College of Medicine, National
Cheng Kung University, Tainan 701, Taiwan
e Advanced Optoelectronic Technology Center and Center for Micro/Nano Science and Technology,
National Cheng Kung University, Tainan 701, Taiwan
[email protected]
Biomaterials Volume 34, Issue 32, Pages 7873–7883 (2013)
Hyperthermia (or thermotherapy) is one alternative cancer therapy available for advanced
disease states. Experimental results showed that by exposing tumor to temperature
around 41-45C for a period of time can damage or kill cancer cells while only minimally
injure normal tissue (Hartman 2008). Cancer lesions present intrinsic acidity and low
oxygen environment which provide resistance to chemotherapy and radiation. These
factors also render cancer cells more sensitive to heat.1
Nanoparticles were known to display unique chemical and physical properties once the
bulk states. Moreover, the size of nanoparticle can readily penetrate into tissue or even subcellular space.
Nanoparticles tailored for many biomedical application such as contrast enhancement in MRI, optical imaging,
ultrasonography and other modalities have been developed or on market in the past decades. Currently, clinical
obstacle for hyperthermia treatment is due to inefficient delivery of enough heat to deep-seated tumor. Application
using superparamagnetic iron oxide nanoparticles for magnetic hyperthermia is believed to be one promising
treatment for cancers. Under the exposure of magnetic field, the individual superparamagnetic nanoparticle with
single magnet dipole dissipate heat due to main dipole relaxation.2 Although a number of magnetic hyperthermia
has been performed by research groups, reports up to date have either described in situ injection of large dosage of
iron oxide nanoparticles or long-term exposure of radio-frequency. 3
We developed octahedron iron oxide nanoparticle is capable of targeting Her-2 and can be thermal-triggered to
release drug under radiofrequency exposure. Upon radiofrequency exposure, our iron oxide nanoparticles present
much higher temperature raise than the commercially available Resovist under 1.3MHz frequency (Fig 1.)
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Figure 1. Fe3O4 nanocrystal has better temperature rise in comparison with commercial Resovist4
After successful modification of the Fe3O4@anti-HER2 nanoparticles to carry 5-FU drugs, intravenous injection
was done to the tumor bearing SCID mice. The synchronized locoregional hyperthermia combined with
chemotherapy by radiofrequency trigger was done 24 hour post injection. We observed that accumulation of iron
oxide to tumor tissue was greatly increased after RF exposure (Fig 2, Left image). Additionally, under thermal
camera image we observed hyperthermia induced in solid tumor mass was evident (Fig 2, Right image).
Figure 2. Iron stain analysis of the tumor mass after radiofrequency treatment (left) and the thermo image during
the treatment (right4).
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We observed that after intravenous injection of anti-Her2 conjugated 5-FU tathered magnetite nanoparticles and
radiofrequency exposure, the tumor size on mice significantly regressed as compared to the control groups (Figure
3). This is the first report to prove the concept that locoregional hyperthermia combined with 5-fluorouracil
chemotherapy can improve cancer therapy and potentially lower down side effects. This article was published in
Biomaterial 2013.
Figure 3. Animal study showed that when synchronized hyperthermia with chemotherapy can enhance tumor
regression.
Reference
1. Moyer, H. R. and K. A. Delman (2008). "The role of hyperthermia in optimizing tumor response to regional
therapy." Int J Hyperthermia 24(3): 251-261.
2. Hartman, K. B. W., Lon J.1; Rosenblum, Michael G.2 (2008). "Detecting and Treating Cancer with
Nanotechnology." Molecular Diagnosis &Therapy 12: 1-14.
3. Rachakatla, R. S., S. Balivada, et al. (2010). "Attenuation of mouse melanoma by A/C magnetic field after
delivery of bi-magnetic nanoparticles by neural progenitor cells." ACS Nano 4(12): 7093-7104.
4. Li, TS., Huang CC., Ruan PW., Chuang KY., Huang KJ., Shieh DB., Yeh CS. (2013). “In vivo anti-cancer
efficacy of magnetite nanocrystal - based system using locoregional hyperthermia combined with 5fluorouracil chemotherapy.” Biomaterials 34, 7873–7883.
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